一氧化氮增加人软骨肉瘤细胞表达基质金属蛋白酶-13的机制研究

The study on the mechanism of matrix metalloproteinase-13 induced by nitric oxide in SW1353 cells

目的研究一氧化氮(NO)是否通过MAPK和NF-κB通路增加基质金属蛋白酶-13(MMP-13)的表达,探讨骨关节炎(OA)发病机制中NO的作用。方法购买并传代人软骨肉瘤细胞(SW1353),用不同浓度的NO供体MAHMA-NONOate刺激后检测MMP-13以及MAPK和NF-κB通路中的蛋白激酶的表达水平。用不同浓度的MAPK和NF-κB通路中的蛋白激酶的抑制剂预先处理细胞后,再用MAHMA-NONOate刺激细胞,再次检测MMP-13以及MAPK和NF-κB通路中的蛋白激酶的表达水平。结果 MAHMA-NONOate增加了细胞MMP-13的表达水平,同时也增加了MAPK和NF-κB通路中的蛋白激酶的活性水平,MAPK家族中的JNK的抑制剂SP600125可以抑制MMP-13的表达水平,NF-κB的抑制剂SN5O也可以抑制MMP-13的表达水平。结论 NO可以通过MAPK家族中的JNK和NF-κB通路增加MMP-13的表达。

Objective To investigate the expression mechanism of matrix metalloproteinase-13 （MMP-13） induced by nitric oxide （NO）,and analysis the role of NO in the development of osteoarthritis.Methods Human chondrosarcoma cells （SW1353） were treated with the NO donor MAHMA-NONOate,then the expression of matrix metalloproteinase-13 （MMP-13）,MAPK and NF-κB were detected.The cells were pretreated with inhibitors of MAPK and NF-κB,and were treated with MAHMA-NONOate thereafter.The expression of matrix metalloproteinase-13 （MMP-13）,MAPK and NF-κB were detected again.Results MAHMA-NONOate increased the expression of MMP-13,MAPK and NF-κB.The inhibitor of JNK,a member of MAPKs,SP600125 inhibited the expression of MMP-13.Besides,the inhibitor of NF-κB,SN50 also inhibited the expression of MMP-13.Conclusions JNK and NF-κB may mediate the expression of MMP-13 induced by NO.